The purpose of this study is to identify neuroendocrine mechanisms of developmental massage therapy (DMT) in preterm infants (<37 weeks gestation). Preterm infants experience stress due to illness and/or routine care. Immediate adverse effects of stress include increases in circulating cortisol, heart and respiratory rates, and hypoxemia and long-term effects include poor postnatal growth, suppression of the immune system, and impaired learning. Thus, the physiological stability is crucial to the preterm infant's well-being. Physiologic stability is dependent upon the sympathetic (SNS) and parasympathetic (PNS) branches of the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis of the endocrine system. PNS develops later in gestation (~37-38 weeks) and younger infants (<36 weeks) tend to have an overriding SNS which leads to physiological instability and a sustained stress response. `Touch'or massage therapy is associated with decreased cortisol levels and improved weight gain in premature infants. Well-designed, randomized controlled clinical trials to evaluate the physiological and neuroendocrine mechanisms of massage therapy in premature infants are needed to: 1) further our understanding of postnatal growth and development and 2) ultimately promote the integration of a massage therapy with conventional medical care. We plan to study the interrelationship of the ANS and HPA axis in premature infants to assess how developmental massage therapy (DMT) modulates physiologic stability and promote postnatal growth. The central hypothesis of this proposal is that DMT is associated with a state of decreased cortisol production and increased PNS tone and insulin-like growth factor 1 (IGF-1) expression leading to improved postnatal growth in premature infants. In the process of testing this hypothesis, we expect to determine the mechanisms by which developmental massage therapy improves PNS tone and IGF-1 expression. Our hypothesis will be tested by the following specific aims: #1) We will determine ANS balance, measured by heart rate variability, before, during, and after DMT;#2) We will compare the relationships between ANS balance and HPA response before and after DM;and #3) We will evaluate somatotrophic (growth hormone and IGF-1) axis response in premature infants who receive DMT. The purpose of this study is to identify neuroendocrine mechanisms of developmental massage therapy (DMT) in preterm infants (<37 weeks gestation). PUBLIC HEALTH RELEVANCE: Preterm infants experience stress due to illness and/or routine care. Immediate adverse effects of stress include increases in circulating cortisol, heart and respiratory rates, and hypoxemia and long-term effects include poor postnatal growth, suppression of the immune system, and impaired learning. Thus, the physiological stability is crucial to the preterm infant's well-being. Physiologic stability is dependent upon the sympathetic (SNS) and parasympathetic (PNS) branches of the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis of the endocrine system. PNS develops later in gestation (~37-38 weeks) and younger infants (<36 weeks) tend to have an overriding SNS which leads to physiological instability and a sustained stress response. Massage therapy is associated with decreased cortisol levels and improved weight gain in premature infants. Well-designed, randomized controlled clinical trials to evaluate the physiological and neuroendocrine mechanisms of massage therapy in premature infants are needed to: 1) further our understanding of postnatal growth and development and 2) ultimately promote the integration of a massage therapy with conventional medical care. We plan to study the interrelationship of the ANS and HPA axis in premature infants to assess how developmental massage therapy (DMT) modulates physiologic stability and promote postnatal growth. The central hypothesis of this proposal is that DMT is associated with a state of decreased cortisol production and increased PNS tone and insulin-like growth factor 1 (IGF-1) expression leading to improved postnatal growth in premature infants. In the process of testing this hypothesis, we expect to determine the mechanisms by which developmental massage therapy improves PNS tone, IGF-1 activity, and postnatal growth. Our hypothesis will be tested by the following specific aims: #1) We will determine ANS balance, measured by heart rate variability, before, during, and after DMT;#2) We will compare the relationships between ANS balance and HPA response before and after DM;and #3) We will evaluate somatotrophic (growth hormone and IGF-1) axis response in premature infants who receive DMT. These types of clinical trials will then direct basic research studies of neuroendocrine mechanisms of massage therapy and lead to: 1) strategies to enhance physiologic stability and postnatal growth and 2) new mechanistic insights about ANS/HPA maturation and its dysregulation in premature infants.